Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis
August
Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis
Jainn-Jim Lin 0 1 2
Hsiang-Ju Hsiao 1 2
Oi-Wa Chan 1 2
Yu Wang 1 2
Shao-Hsuan Hsia 1 2
Cheng-Hsun Chiu 0 1
0 Molecular Infectious Disease Research Center, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, 4 Department of Pediatrics, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University , Taoyuan, Taiwan , 5 Department of Pediatrics, Chang Gung Memorial Hospital , Chiayi , Taiwan
1 Editor: Dermot Cox, Royal College of Surgeons in Ireland , IRELAND
2 Division of Pediatric Critical Care and Pediatric Sepsis Study Group, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, 2 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University , Taoyuan , Taiwan
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Data Availability Statement: All relevant data are
within the manuscript.
Funding: This research was a part of an infection
and immunity sepsis project, and was performed
by the Pediatric Sepsis Study Group at Chang
Gung Children's Hospital in Taoyuan, Taiwan. The
work was supported in part by grants from Chang
Gung Memorial Hospital (grant: CMRPG3B0841,
CMRPG3B0842 and CMRPG3B0843), Taiwan. The
funder had no role in study design, data collection
Background
lial injury.
Objective
mortality.
Methods
Results
Endothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothe
The aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and
and analysis, decision to publish, or preparation of
the manuscript.
Competing interests: The authors have declared
that no competing interests exist.
Abbreviations: DIC, disseminated intravascular
coagulation; ELISA, enzyme-linked immunosorbent
assay; PELOD, Pediatric Logistic Organ
Dysfunction; PICU, pediatric intensive care unit;
PMOD, Pediatric-Multiple Organ Dysfunction;
PRISM, Pediatric Risk of Mortality.
mU/ml (IQR: 0.5±6)] (p = <0.001 and 0.001, respectively). There was also a significant positive
correlation between serum thrombomodulin level on day 1 and day 1 PRISM-II, PELOD,
P
MOD and DIC scores. The patients who died had significantly higher serum thrombomodulin levels on days 1 and 3 [day 1: median, 9.9 mU/ml (IQR: 6.2±15.6) and day 3: median, 10.4 mU/ml (IQR: 9.2±11.7)] than the survivors [day 1; median, 4.4 mU/ml (IQR: 2.2±7.5) and day 3: [median, 3.5 mU/ml (IQR: 1.6±5.7)] (p = 0.046 and 0.012, respectively).
Conclusion
Introduction
Increased serum thrombomodulin levels were found in different pediatric sepsis syndromes and correlated with disease severity and mortality.
Treating sepsis is a challenge, and it is one of the leading causes of admissions to pediatric
intensive care units. The initial manifestation can often be nonspecific and misleading. Severe
sepsis is frequently complicated by disseminated intravascular coagulation (DIC) and multiple
organ dysfunction syndromes (MODS). Deterioration from sepsis to septic shock and MODS
most often occurs in the first 24 hours [
1
]. In our previous study, we found decreased a
disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS 13)
activity is associated with disease severity and outcome in pediatric severe sepsis [
2
].Despite an
improved understanding of the pathophysiology of sepsis, the overall mortality rate remains
unacceptably high [
3
].
Endothelial dysfunction plays an important role in the pathophysiology of sepsis.
Thrombomodulin, a membrane glycoprotein, is expressed on vascular endothelial cells and is found
in the body in a bound form and a soluble or plasmatic form [
4
]. It binds to thrombin and acts
as an anticoagulant. Once thrombomodulin binds to endothelial thrombin, the
thrombinthrombomodulin complex accelerates protein C activation [
4, 5
], and soluble
thrombomodulin is released from the surface of endothelial cells into the serum by proteolytic degradation
[6]. As previously reported, the serum thrombomodulin is elevated in diseases associated with
endothelial injury, such as acute respiratory distress syndrome [
7,8
], disseminated
intravascular coagulation [9], and organ dysfunction induced by sepsis [10±12]. Therefore,
thrombomodulin is known to be a biomarker of endothelial injury.
Since endothelial dysfunction plays an essential role in the pathogenesis of sepsis, some
studies have focused on serum thrombomodulin level as a predictor of the severity of sepsis
and mortality in adults [10±12]. However, few pediatric studies have examined the role of
serum thrombomodulin as a biomarker to predict the clinical course of different (...truncated)